This application relates to the synthesis of novel synthetic peptides and in particular to the synthesis of growth hormone-releasing factors (GRF) and their non-naturally occuring analogs.
Growth hormone is one of the hormones secreted by the anterior pituitary. The presence of excess of growth hormone can cause giantism or acromegaly and insufficient secretion causes dwarfism. It effects the metabolism of protein as well as the metabolism of carbohydrates and lipids, and has been described as switching the source of fuel for the body from carbohydrate to fat. Human growth hormone has limited application as a treatment for puituitary dwarfism; see Goodman and Gilman, The Pharmacological Basis of therapeutics, 5th Edition, pp. 1376-1382 (1975).
Adenohypophysial function, including growth hormone (GH) secretion, is mediated by neurohumoral substances referred to as releasing and release inhibiting hormones or factors. Growth hormone secretion is stimulated by growth hormone-releasing factor (GRF). Peptides with GRF activity were isolated from human pancreatic tumor and the structure of this natural peptide was elucidated; Guillemin et al, Science 218: 582 (1982) and Rivier et al, Nature 300: 276 (1982). Considerable interest has developed in the identification and characterization of hypothalamic GRF and in their potential use as therapeutic and diagnostic agents. For instance, human pancreatic tumor GRF (hpGRF), having a known structure, undergoes a drastic loss of biological activity during storage or when introduced into a living system. This loss of activity is believed to be, at least partly, caused by the oxidation of methionine, an amino acid present in the 27th position of naturally occurring hpGRF.